Evaluation And Preliminary Efficacy Studies On Isoquinoline Alkaloids Of Medicinal Rhizomes And Non-medicinal Fibrous Roots Of Sichuan Coptidis Rhizoma

Coptidis Rhizoma is a perennial traditional Chinese medicinal material with the efficacy of clearing heat and drying dampness,purging fire and detoxification,which is recorded in the 2020 edition of "People’s Republic of China Pharmacopoeia"(1).The rhizomes of Coptidis Rhizoma is mostly used as medicine.Because of its 4～5 years growth cycle and strict growth environment requirements,it has been in a situation of "supply shortage" in the market,resulting in the price of the rhizomes of Coptidis Rhizoma increased year by year.The fibrous roots,as a non-medicinal part of Coptidis Rhizoma,is mostly discarded.It has not been recorded in the previous edition of Pharmacopoeia,and only Standard for Chinese Medicinal Materials in Guangdong Province(2011 edition)is included in the drug.Fibrous roots of Coptidis Rhizoma contains alkaloids and pharmacological effects similar to the rhizomes of Coptidis Rhizoma,which has high research value,and the dry weight is large and the waste quantity is large.In-depth study is urgently needed to reduce the waste of plant resources of Coptidis Rhizoma and improve economic benefits.(1)In this study,it was established the content determination method of 6 main isoquinoline alkaloids in medicinal rhizomes/non-medicinal fibrous roots of Coptidis Rhizoma,and compared and analyzed different medicinal parts and underground resources of Coptidis Rhizoma.The methodological verification showed that this method had good precision,good stability and good reproducibility.It was found that there were also six major isoquinoline alkaloids in the different parts of Coptidis Rhizoma at different ages and fibrous roots of Coptidis Rhizoma from different habitats,but the content distribution was different.The dry weights of 3～5 years old fibrous roots of Weilian and Yalian accounted for9.02%～14.93% and 16.16%～26.39% of the total medicinal materials,and 48.69%～88.50 %and 11.50%～55.31% of the underground parts.It was found that the fibrous roots of Coptidis Rhizoma can be distinguished by character description,powder microscopic characteristics and TLC identification.The water content,total ash content and extract content of the 22 batches of fibrous root samples of Coptidis Rhizoma were 5.94%～11.60%,6.26%～12.52%and 9.10%～15.37%.And the similarity was > 0.900,it has good consistency.And it found that the main components affecting the quality of fibrous roots of Coptidis Rhizoma were jatrorrhizine,epiberberine,coptisine,palmatine and berberine by chemical pattern recognition.(2)In this study,the mechanism of isoquinoline alkaloids in medicinal rhizomes/non-medicinal fibrous roots of Coptidis Rhizoma in the treatment of type 2diabetes mellitus(T2DM)was predicted by network pharmacology,and 10 target compounds,10372 T2 DM targets and 32 core targets were screened.It was found that GO biological function enrichment was involved in 2787 aspects such as phosphotransferase activity alcohol group as acceptor,receptor complex and positive regulation of transferase activity,etc.And KEGG pathway enrichment mainly involved in 348 pathways such as cancer pathway,Th17 cell differentiation and insulin resistance,etc.It was found that the isoquinoline alkaloids of Coptidis Rhizoma such as(R)-Canadine,berberrubine,berlambine,berberine and jatrorrizine has good binding ability with PIK3 CA,PIK3R1,SRC,STAT3 and MCHR1 by molecular docking verification.It is concluded that Coptidis Rhizoma plays a role in T2 DM through “multiple components-multiple targets-multiple pathways”.Then the rat model of type 2 diabetes mellitus was established and validated in vivo.It showed that the medicinal rhizomes / non-medicinal fibrous roots of Weilian,berberine and jatrorrhizine could improve hepatic lipid metabolism disorder and protect liver injury in type 2 diabetic rats.